1. Field of the Invention
Morphine is a well known narcotic analgesic having the structural formula: ##STR2##
The compound of this invention is structurally related to morphine and is named according to the morphinan system of nomenclature using the morphinan nucleus which is shown below: ##STR3## The numbering and stereochemical placement of atoms in the morphinan system is the same as that depicted for morphine. A dashed line is used to represent a covalent bond projecting below the plane of a reference atom while a wedged or heavily accented line signifies a covalent bond above such plane. The compound of this invention has the same stereochemical placement of atoms as depicted for morphine in those positions where the stereochemistry is not depicted by a dashed or wedged line.
Morphine and its structurally related relatives are used primarily as analgesics. While extremely effective for the relief of moderate to severe pain these compounds are narcotic and most possess dependence-inducing ability and produce other side effects such as emesis, constipation, sweating, respiratory depression and myosis which make then less than ideal analgesics. It is impossible to predict, based on structure alone, whether a particular morphine-like compound will act as an analgesic (agonist), a narcotic antagonist or possess a combination of these properties since very minute structural modifications in the molecule result in significant changes in pharmcological activity. A compound with the appropriate profile of analgesic (agonist) and narcotic antagonist actions has potential for treatment of moderate to severe pain without the liability of drug dependence or drug abuse.
2. Prior Art
17-alkyl or cycloalkyl-4,5.alpha.-epoxy-3-substituted-14-hydroxy morphinan-6-one compounds corresponding to the formula: ##STR4## Where R is H or methyl are known. Thus, the foregoing formula represents oxycodone when R and R.sup.1 are methyl and oxymorphone when R is H and R.sup.1 is methyl. Both of these compounds are known to be useful as narcotic analgesics. The foregoing formula represents naloxone when R is H and R.sup.1 is allyl and naltrexone when R is H and R.sup.1 is cyclopropylmethyl.
Blumberg et al. disclose in Narcotic Antagonists (1974) Pp 33-43 a compound of the formula: ##STR5##
This compound is said to exhibit analgesic activity, having an ED.sub.50 of 0.39 mg/kg, and narcotic antagonist activity having an ED.sub.50 of 0.57 mg/kg in counteracting the action of oxymorphone.
The compound of the present invention possesses potent analgesic activity and has demonstrated narcotic antagonist activity.